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Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
Associations between circulating proteins and corresponding genes expressed in coronary thrombi in patients with
Ragnhild Helseth1, Thomas W Weiss2, Trine Baur Opstad1
1Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
Insights
Circulating biomarkers in acute myocardial infarction (AMI) do not consistently reflect local gene expression in coronary thrombi or total ischemic time. These findings suggest a localized environment within atherothrombosis, potentially guiding targeted therapies.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biomarker Discovery
Background:
- Acute myocardial infarction (AMI) involves dynamic gene expression in coronary thrombi.
- The relationship between circulating biomarkers, local gene expression, and ischemic time in AMI is not well understood.
- Investigating soluble biomarkers' association with thrombi genes and ischemic duration is crucial for understanding AMI pathophysiology.
Purpose of the Study:
- To determine if circulating biomarkers correlate with gene expression in coronary thrombi.
- To assess the association between circulating biomarkers and total ischemic time in AMI patients.
- To explore the localized nature of the atherothrombotic environment.
Main Methods:
- Blood samples were collected from 33 AMI patients undergoing percutaneous coronary intervention (PCI).
- A panel of biomarkers related to plaque rupture, platelet/endothelial activation, hemostasis, and inflammation were analyzed.
- Proximity Extension Assay (Proseek Multiplex CVD I), ELISAs, and RT-PCR were employed for laboratory analyses.
Main Results:
- Circulating P-selectin showed correlation with corresponding P-selectin gene expression in thrombi (r=0.530, p=0.002).
- Plasma galectin 3, fractalkine, monocyte chemoattractant protein 1 (MCP-1), and caspase 8 inversely correlated with ischemic time (p <0.05).
- Higher levels of plasma MCP-1, galectin 3, and epidermal growth factor (EGF) were observed in patients with shorter ischemic times (≤ 4 hours).
Conclusions:
- Dynamic changes in circulating mediators were not mirrored by locally expressed genes in coronary thrombi.
- The study suggests a confined biological milieu at the site of atherothrombosis.
- These findings may have implications for developing selective therapeutic strategies in AMI.
Introduction:
Several genes are expressed in aspirated coronary thrombi in acute myocardial infarction (AMI), exhibiting dynamic changes along ischemic time. Whether soluble biomarkers reflect the local gene environment and ischemic time is unclear. We explored whether circulating biomarkers were associated with corresponding coronary thrombi genes and total ischemic time.
Material And Methods:
In 33 AMI patients undergoing percutaneous coronary intervention (PCI), blood samples were collected within 6-24h for markers related to plaque rupture (metalloproteinase 9, tissue inhibitor of metalloproteinases 1), platelet and endothelial cell activation (P-selectin, CD40 ligand, PAR-1), hemostasis (tissue factor, tissue plasminogen activator, plasminogen activator inhibitor 1, free and total tissue factor pathway inhibitor, D-dimer, prothrombin fragment 1+2), inflammation (interleukin 8 and 18, fractalkine, monocyte chemoattractant protein 1 (MCP-1), CXCL1, pentraxin 3, myeloperoxidase) and galectin 3, caspase 8 and epidermal growth factor (EGF). Laboratory analyses were performed by Proximity Extension Assay (Proseek Multiplex CVD I(96 × 96)), ELISAs and RT-PCR.
Results:
Only circulating P-selectin correlated to the corresponding P-selectin gene expression in thrombi (r=0.530, p=0.002). Plasma galectin 3, fractalkine, MCP-1 and caspase 8 correlated inversely to ischemic time (r=-0.38-0.50, all p <0.05), while plasma MCP-1, galectin 3 and EGF were higher at short (≤ 4 h) vs. long (>4h) ischemic time (all p <0.05).
Conclusions:
The dynamic changes in circulating mediators along ischemic time were not reflected in the profile of locally expressed genes. These observations indicate a locally confined milieu within the site of atherothrombosis, which may be important for selective therapy.
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